En undersøgelse af Selexipag som tilføjelsesbehandling til standardbehandling hos børn med pulmonal arteriel hypertension (SALTO)
En randomiseret, multicenter, dobbeltblind, placebokontrolleret, parallelgruppe, hændelsesdrevet, gruppesekventiel undersøgelse med åben forlængelsesperiode for at vurdere effektiviteten og sikkerheden af Selexipag som tilføjelsesbehandling til standarden for pleje hos børn Alder >=2 til
The purpose of this study is to evaluate whether the addition of selexipag to standard of care treatment delays disease progression in children with Pulmonary Arterial Hypertension (PAH) in comparison to placebo.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Detaljeret beskrivelse
Pediatric PAH is a rare and progressive disorder associated with considerable morbidity and mortality. Given the significant medical need to develop treatments in children with PAH, further clinical studies in the pediatric population are therefore needed to provide more data for the management of PAH in children. Selexipag (JNJ-67896049) is an orally available, selective, and long-acting non-prostanoid agonist of the prostacyclin receptor approved and commercially available for the treatment of adult participants with PAH. Selexipag and its metabolite possess anti-fibrotic, anti-proliferative, and anti-thrombotic properties. Currently, no medicines targeting prostacyclin pathway are approved for pediatric use in PAH. An effective and orally available therapy acting on the prostacyclin receptor such as selexipag introduced at medically appropriate stage of PAH disease, and primarily in combination with current first-line oral PAH-specific medicines in participants in need of additional therapy because of insufficient disease control would represents a major advance to the therapeutic management of PAH pediatric participants. This study consists of a screening period of up to 6 weeks and a double-blind treatment period, including up-titration and maintenance periods, followed by a 3-year open-label extension period (OLEP) and a 30-day safety follow-up period that occurs after the last dose of study intervention (either double-blind or open-label). Safety, pharmacokinetic and efficacy assessments will be performed during the study. An Independent Data Monitoring Committee (IDMC) will be established to monitor data on an ongoing basis, to review interim data, and to ensure the continuing safety of the participants enrolled in this study. The approximate duration of the study is 8 years.
Undersøgelsestype
Undersøgelsestype
Tilmelding (Faktiske)
Tilmelding
Fase
Fase
- Fase 3
Kontakter og lokationer
Studiesteder
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South Brisbane, Australien, 4101
- Queensland CHILDREN'S HOSPITAL
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Brussels, Belgien, 1070
- ULB Hôpital Erasme
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Ghent, Belgien, 9000
- Universitair Ziekenhuis Gent
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Leuven, Belgien, 3000
- Universitaire Ziekenhuizen Leuven
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Blumenau, Brasilien, 89030-101
- Complexo de Prevencao,Diagnostico,Terapia e Reabilitacao Respiratoria LTDA Hospital Dia do Pulmao
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Brasília, Brasilien, 70310-500
- Fundacao Universitaria de Cardiologia - Instituto de Cardiologia e Transplantes do DF
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Curitiba, Brasilien, 80250-060
- Hospital Pequeno Principe
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Fortaleza, Brasilien, 60840-285
- Secretaria da Saude do Estado do Ceara - Hospital Doutor Carlos Alberto Studart Gomes
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Porto Alegre, Brasilien, 90020-090
- Irmandade Santa Casa de Misericordia de Porto Alegre
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Porto Alegre, Brasilien, 90620-001
- Fundacao Universitaria de Cardiologia
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São Paulo, Brasilien, 01221-020
- Irmandade Santa Casa de Misericordia de Sao Paulo
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São Paulo, Brasilien, 04024 002
- SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
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Sofia, Bulgarien, 1309
- Multiprofile Hospital For Active Treatment National Cardiology Hospital, Ead
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Alberta
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Edmonton, Alberta, Canada, T6G 2B7
- Stollery Children's Hospital
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Ontario
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Toronto, Ontario, Canada, M5G 1X8
- Hospital For Sick Children
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Bogotá, Colombia, 0000000
- Clinica San Rafael
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Bogotá, Colombia, 0000000
- Fundacion Neumologica Colombiana
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Bogotá, Colombia
- Fundacion Santa Fe de Bogota
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Cali, Colombia, 760042
- Clínica Imbanaco S.A.S.
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Piedecuesta, Colombia, 681017
- Fundacion Cardiovascular de Colombia
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Soledad, Colombia, 0000000
- Hospital Universidad del Norte
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Helsinki, Finland, 29
- New Children's Hospital of the Helsinki University Hospital (HUS)
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Arizona
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Phoenix, Arizona, Forenede Stater, 85016
- Phoenix Children's Hospital
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California
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Los Angeles, California, Forenede Stater, 90095
- UCLA Medical Center
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San Francisco, California, Forenede Stater, 94158
- UCSF
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Colorado
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Aurora, Colorado, Forenede Stater, 80045
- Childrens Hospital Colorado
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District of Columbia
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Washington D.C., District of Columbia, Forenede Stater, 20010
- Children's National Medical Center
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Florida
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Gainesville, Florida, Forenede Stater, 32610
- Congenital Heart Center of the University of Florida
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Indiana
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Indianapolis, Indiana, Forenede Stater, 46202
- Riley Hospital for Children
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Michigan
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Detroit, Michigan, Forenede Stater, 48201
- Detroit Medical Center
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Ohio
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Cincinnati, Ohio, Forenede Stater, 45229
- Cincinnati Children's Hospital Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, Forenede Stater, 19104
- Childrens Hospital Of Philadelphia
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Texas
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Houston, Texas, Forenede Stater, 77030
- Texas Children's Hospital
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Utah
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Salt Lake City, Utah, Forenede Stater, 84113
- Primary Children's Hospital
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Virginia
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Charlottesville, Virginia, Forenede Stater, 22908
- University of Virginia Division of Pediatric Cardiology
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Lille, Frankrig, 59037
- Hôpital Cardiologique - Chru Lille
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Marseille, Frankrig, 13385
- Hopital de la Timone
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Montpellier, Frankrig, 34295
- CHU Arnaud de Villeneuve
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Paris, Frankrig, 75015
- Hôpital Necker - Enfants Malades
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Pessac, Frankrig, 33604
- Hôpital Cardiologique Du Haut-Lévêque
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Toulouse, Frankrig, 31059
- Chu Hopital Des Enfants
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Minsk, Hviderusland, 220013
- State Institution Republican Scientific And Practical Center For Pediatric Surgery
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Minsk, Hviderusland, 220118
- Health Institution 4Th City Children'S Clinical Hospital
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Dublin, Irland
- Our Lady's Children's Hospital
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Haifa, Israel, 3109601
- Rambam Medical Center
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Ramat Gan, Israel, 52621
- Sheba Medical Center
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Bologna, Italien, 40138
- Azienda Ospedaliera Policlinico S. Orsola-Malpighi
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Milan, Italien, 20162
- ASST Grande Ospedale Metropolitano Niguarda
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Padova, Italien
- Universta Degli Studi Di Padova
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Roma, Italien, 00193
- Ospedale Pediatrico Bambin Gesù
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S. Donato Milanese, Italien, 20097
- IRCCS Policlinico San Donato
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Torino, Italien, 10126
- AOU Città della Salute e della Scienza di Torino, Presidio Ospedale Infantile Regina Margherita
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Beijing, Kina, 100029
- Beijing Anzhen Hospital
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Guangzhou, Kina, 510623
- Guangzhou Women And Childrens Medical Center
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Qingdao, Kina, 266000
- Qingdao Women and Children's Hospital
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Qingdao, Kina, 266000
- Qingdao Women and Children's Hospital 1
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Shanghai, Kina, 200127
- Shanghai Childrens Medical Center
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Shanghai, Kina, 201102
- Children S Hospital of Fudan University
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Shenyang, Kina, 110000
- The General Hospital of Northern Theater Command
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Vilnius, Litauen, LT08661
- Vilnius University Hospital Santariskiu Clinics
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Kuala Lumpur, Malaysia, 50400
- National Heart Institute
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Guadalajara, Mexico, 44160
- CICUM San Miguel
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Monterrey, Mexico, 64718
- Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)
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México, Mexico, 52787
- Operadora de Hospitales Angeles SA de CV Hospital Angeles Lomas
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Gdansk, Polen, 80 952
- Uniwersyteckie Centrum Kliniczne
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Krakow, Polen, 30-663
- Uniwersytecki Szpital Dzieciecy w Krakowie
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Poznan, Polen, 60 572
- Szpital Kliniczny im Karola Jonschera
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Warsaw, Polen, 04-730
- Instytut Pomnik Centrum Zdrowia Dziecka
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Wroclaw, Polen, 51 124
- Wojewodzki Szpital Specjalistyczny we Wroclawiu
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Zabrze, Polen, 41-800
- Slaskie Centrum Chorob Serca
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Lisbon, Portugal, 1169-024
- Uls Sao Jose - Hosp. Santa Marta
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Porto, Portugal, 4200 319
- Uls Sao Joao - Hosp. Sao Joao
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Kazan', Rusland, 420012
- Kazan State Medical University
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Kazan', Rusland, 420059
- Kazan State Medical University 1
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Kemerovo, Rusland, 650002
- Scientific and Research Institution of Cardiovascular Diseases Complex Problems
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Moscow, Rusland, 125373
- Childrens City Clinical Hospital n.a. Bashlyaeva
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Moscow, Rusland, 125412
- Veltischev Research and Clinical Institute for Pediatrics of the Pirogov RNRMU
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Samara, Rusland, 443070
- Samara Regional Clinical Cardiological Dispensary
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Lausanne, Schweiz, 1011
- Centre Hospitalier Universitaire Vaudois CHUV
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Belgrade, Serbien, 11000
- Univerzitetska Dečja Klinika
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A Coruña, Spanien, 15006
- Hosp Univ A Coruna
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Barcelona, Spanien, 08035
- Hosp Univ Vall D Hebron
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Esplugues de Llobregat, Spanien, 08950
- Hosp. Sant Joan de Deu
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Madrid, Spanien, 28046
- Hosp. Univ. La Paz
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Madrid, Spanien, 28009
- Hosp. Gral. Univ. Gregorio Maranon
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Seville, Spanien, 41013
- Hosp. Virgen Del Rocio
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Gothenburg, Sverige, 416 50
- Drottning Silvias barn- och ungdomssjukhus
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Lund, Sverige, 222 42
- Skanes universitetssjukhus
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Seoul, Sydkorea, 03080
- Seoul National University Hospital
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Seoul, Sydkorea, 06351
- Samsung Medical Center
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Seoul, Sydkorea, 120-752
- Severance Hospital Yonsei University Health System
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Yangsan, Sydkorea, 50612
- Pusan National University Yangsan Hospital
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Kaohsiung City, Taiwan, 813414
- Kaohsiung Veterans General Hospital
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Tainan, Taiwan, 704
- National Cheng Kung University Hospital
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Taipei, Taiwan, 100
- National Taiwan University Hospital
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Chiang Mai, Thailand, 50200
- Chiang Mai University Hospital
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Songkhla, Thailand, 90110
- Songklanagarind hospital
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Adana, Tyrkiet (Türkiye), 01790
- Cukurova Balcali Hospital Application and Research Center
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Ankara, Tyrkiet (Türkiye), 06230
- Hacettepe University Medical Faculty
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Istanbul, Tyrkiet (Türkiye), 34093
- CAPA Istanbul University Medical Faculty
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Istanbul, Tyrkiet (Türkiye), 34303
- Mehmet Akif Ersoy Training and Research Hospital
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Izmir, Tyrkiet (Türkiye), 35020
- Izmir Tepecik Training and Research Hospital
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Izmir, Tyrkiet (Türkiye), 35210
- Behcet Uz Pediatric Diseases and Surgery Training and Research Hospital
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Freiburg im Breisgau, Tyskland, 70106
- Universitätsklinikum Freiburg Zentrum
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Heidelberg, Tyskland, D-69120
- Universitaetsklinikum Heidelberg
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Leipzig, Tyskland, 04289
- Herzzentrum Leipzig GmbH
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München, Tyskland, 81377
- Klinikum der Universitaet Muenchen
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Dnipro, Ukraine, 49006
- Dnipropetrovsk clinical medical center of Mother and Child after prof. Rudnev
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Dnipro, Ukraine, 49070
- MI 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiac Surgery'
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Kyiv, Ukraine, 04050
- Scientific Practical Medical Center for Pediatric Cardiology and Cardio Surgery of the MOH
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Zaporizhzhya, Ukraine, 69063
- MI Zaporizhzhia Regional Clinical Childrens Hospital of Zaporizhzhia Regional Council
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Budapest, Ungarn, 1096
- Gottsegen György Országos Kardiológiai Intézet
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Hanoi, Vietnam
- Hanoi Medical University Hospital
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Ho Chi Minh City, Vietnam
- Children's Hospital 1
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Ho Chi Minh City, Vietnam, 700000
- Tam Anh Hospital
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Ho Chi Minh City, Vietnam, 700000
- University Medical Center Ho Chi Minh city
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Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Participants between greater than or equal to (>=) 2 and less than (<) 18 years of age weighing >=9 kilogram (kg) at randomization
- Pulmonary arterial hypertension (PAH) diagnosis confirmed by documented historical right heart catheterization (RHC) performed at any time before participant's screening
- PAH (World Health Organization [WHO] Group 1), including participants with Down syndrome, of the following etiologies: Idiopathic PAH (IPAH); Heritable PAH (HPAH); PAH associated with congenital heart disease (PAH-associated with congenital heart disease [aCHD]) (PAH with coincidental CHD [that is, a small atrial septal defect, ventricular septal defect, or patent ductus arteriosus that does not itself account for the development of elevated PVR] and if approved by the BCAC) and Post-operative PAH (persisting / recurring/ developing >=6 months after repair of CHD); Drug or toxin-induced; PAH associated with Human immunodeficiency virus (HIV)
- WHO functional class (FC) II and III
- Participants treated with at least 1 PAH-specific treatment, example, an Endothelin receptor antagonist (ERA) and/or a Phosphodiesterase type-5 (PDE-5) inhibitor/soluble guanylate cyclase stimulator, provided that the treatment dose(s) has been stable for at least 3 months prior to first dose of study intervention
Exclusion Criteria:
- PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease, and/or pulmonary capillary hemangiomatosis
- PAH associated with Eisenmenger syndrome
- Previous exposure to Uptravi (selexipag)
- Known concomitant life-threatening disease with a life expectancy <12 months
- Pregnant, planning to become pregnant, or lactating
- Known allergies, hypersensitivity, or intolerance to selexipag or its excipients
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Dobbelt
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
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Eksperimentel: Selexipag
Participants will receive selexipag based on the body weight on Day 1 and will continue thereafter with twice daily dosing. Selexipag will be uptitrated during the first 12 weeks until the participants reaches the individual maximum tolerated dose (iMTD) or until a maximum dose corresponding to their baseline body-weight category is achieved. Uptitration is followed by a maintenance period after Week 12 until end of treatment (EOT), at the maximum tolerated dose. Participants will continue to receive pulmonary arterial hypertension (PAH)-specific concomitant therapies such as ERAs, PDE-5 inhibitors, and soluble guanylate cyclase stimulator as per local standard-of-care. |
Selexipag tablet will be administered orally.
Andre navne:
ERAs will be administered as SOC therapy. PDE-5 inhibitor will be administered as SOC therapy. Soluble guanylate cyclase stimulator will be administered as SOC therapy. |
|
Placebo komparator: Placebo
Participants will receive matching placebo based on the body weight on Day 1 and will continue thereafter with twice daily dosing. Participants will continue to receive PAH-specific concomitant therapies such as ERAs, PDE-5 inhibitors, and soluble guanylate cyclase stimulator as per local standard-of-care. |
ERAs will be administered as SOC therapy. PDE-5 inhibitor will be administered as SOC therapy. Soluble guanylate cyclase stimulator will be administered as SOC therapy. Matching placebo tablets will be administered orally. |
|
Eksperimentel: Open-Label Extension Period: Selexipag
Participants with a positive benefit/risk ratio of selexipag for PAH will be offered selexipag in the open label extension period. Participants on selexipag during the double-blind treatment period will continue treatment at their iMTD during the OLEP, for those previously on placebo, the iMTD will uptitrate selexipag during first 12 weeks until participant reaches iMTD. Participants will continue to receive PAH-specific concomitant therapies such as ERAs, PDE-5 inhibitors, and soluble guanylate cyclase stimulator as per local standard-of-care. |
Selexipag tablet will be administered orally.
Andre navne:
ERAs will be administered as SOC therapy. PDE-5 inhibitor will be administered as SOC therapy. Soluble guanylate cyclase stimulator will be administered as SOC therapy. |
Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Double-blind Period: Time to Disease Progression
Tidsramme: Placebo arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 199 weeks); Selexipag arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 213 weeks)
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Time to disease progression: time from randomization to first Clinical Event Committee (CEC)-confirmed disease progression event occurring between date of randomization until double-blind end date (DBED) + 7 days. Disease progression event as adjudicated by CEC, defined as any of the following: death (all causes); atrial septostomy or Potts' anastomosis, or registration on lung transplant list; hospitalization due to worsening pulmonary arterial hypertension (PAH); clinical worsening of PAH. Clinical worsening of PAH was defined as initiation of new PAH-specific therapy or intravenous diuretics or continuous oxygen use and at least 1 of the following: worsening in World Health Organization (WHO) functional class (FC); new occurrence or worsening: of syncope, of at least 2 PAH symptoms (shortness of breath/dyspnea, chest pain, cyanosis, dizziness/near syncope, or fatigue), of signs of right heart failure not responding to oral diuretics. Kaplan-Meier method was used for estimation. |
Placebo arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 199 weeks); Selexipag arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 213 weeks)
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Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Double-blind Period: Change in log2 N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) From Baseline to Week 24
Tidsramme: Baseline (Day 1), Week 24
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Change in log2 NT-proBNP from baseline to Week 24 was reported. Change from baseline to Week 24 in the central laboratory NT-proBNP (nanograms per liter [ng/L]) value, expressed as the log2-transformed ratio of the Week 24 NT-proBNP value over the baseline value: log2 (Week 24 NT-proBNP divided by Baseline NT-proBNP). Clinically, a reduction from baseline in NT-proBNP (ratio < 1) was considered an improvement. The baseline value was the last non-missing assessment obtained before or on the DB start date (DBSD). |
Baseline (Day 1), Week 24
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Double-blind Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious AEs (TESAEs)
Tidsramme: Placebo arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 198.42 weeks); Selexipag arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 212.42 weeks)
|
Number of participants with TEAEs (included serious and non-serious events) and TESAEs during DB period was reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. A serious AE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, or was medically important. TEAEs were defined as any AE occurring on or after the initial administration of study intervention through the day of last dose in the DB treatment period plus 3 days and/or prior to start of OL study administration. |
Placebo arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 198.42 weeks); Selexipag arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 212.42 weeks)
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Double-blind Period: Number of Participants With AEs Leading to Premature Discontinuation of Study Treatment
Tidsramme: Placebo arm: Start of treatment (Day 1) up to last dose in the DB treatment (maximum up to 198 weeks); Selexipag arm: Start of treatment (Day 1) up to last dose in the DB treatment (maximum up to 212 weeks)
|
Number of participants with AEs leading to premature discontinuation of study treatment during DB period was reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. |
Placebo arm: Start of treatment (Day 1) up to last dose in the DB treatment (maximum up to 198 weeks); Selexipag arm: Start of treatment (Day 1) up to last dose in the DB treatment (maximum up to 212 weeks)
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Double-blind Period: Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Tidsramme: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in vital signs parameters: systolic and diastolic blood pressure during DB period was reported. Vital signs were measured after the participant has rested at least 5 minutes in sitting position. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Change From Baseline in Vital Signs: Pulse Rate
Tidsramme: Baseline (Day 1), Weeks 24, 48, 72, and 96
|
Change from baseline in vital signs parameter: pulse rate during DB period was reported. Vital signs were measured after the participant has rested for at least 5 minutes in sitting position. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Change From Baseline in Growth Parameter: Body Weight
Tidsramme: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in growth parameter: body weight during DB period was reported. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Change From Baseline in Growth Parameter: Height
Tidsramme: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in growth parameter: height during DB period was reported. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Number of Participants With Shift From Baseline in Sexual Maturation (Tanner Stage)
Tidsramme: Placebo arm: Baseline (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 198.42 weeks); Selexipag arm: Baseline (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 212.42 weeks)
|
Tanner staging were assessed for pubic hair growth and genitalia development (GD) in males (M) and for pubic hair growth and breast development (BD) in females (F) in stages(S) 1 to 5 and missing data. If a participant had reached Tanner stage 5, no further tanner pubertal stage assessment were to be completed. Tanner stage was assessed in F >=8 years; M >=9 years. Pubic hair growth (M and F) stages: S1: No hair, S2: Downy hair, S3: More coarse and curly hair, S4: Adult-like hair quality; S5: Hair extends to medial surface of thighs. BD in females: S1: Nipple raised a little, rest of breast still flat, S2: Breast bud forms, S3: More elevated, outside areola, S4: Increased breast size, S5: Final adult-size breasts. GD in males: S1: Testes, scrotum, and penis about same size, S2: Enlargement of scrotum, testes, and penis, S3: Enlargement of penis, S4: Penis and glands became larger, S5: Genitalia size and shape same an adult male. Categories with at least 1 non-zero data are reported. |
Placebo arm: Baseline (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 198.42 weeks); Selexipag arm: Baseline (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 212.42 weeks)
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Double-blind Period: Number of Participants With Treatment-emergent Electrocardiogram (ECG) Abnormalities
Tidsramme: Placebo arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 198.42 weeks); Selexipag arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 212.42 weeks)
|
Number of participants with treatment-emergent ECG abnormalities were reported. Any abnormality occurring on or after the initial administration of study intervention through the day of last dose in the DB treatment period plus 3 days was considered to be treatment-emergent. Abnormalities that were not present at baseline were reported. Abnormalities were assessed as per investigator's discretion. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Placebo arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 198.42 weeks); Selexipag arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 212.42 weeks)
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Double-blind Period: Number of Participants With Treatment-emergent (TE) Marked Laboratory Abnormalities
Tidsramme: Placebo arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 198.42 weeks); Selexipag arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 212.42 weeks)
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Number of participants with TE marked laboratory abnormalities during DB period was reported. TE marked laboratory abnormalities included hemoglobin, platelet count, leukocyte count, potassium, calcium, thyrotropin, thyroxine free and triiodothyronine free. Any abnormality occurring or worsening at or after the DB study treatment start date through the DB study treatment end date plus 3 days was considered to be treatment-emergent. If the abnormality was present at baseline, then any post-baseline abnormality was considered treatment-emergent only if the post-baseline abnormality was in a category worse than at baseline. HH, HHH, HHHH = marked abnormally high values; LL, LLL = marked abnormally low values. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Placebo arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 198.42 weeks); Selexipag arm: Start of treatment (Day 1) up to 3 days after last dose in the DB treatment (maximum up to 212.42 weeks)
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Double-blind Period: Change From Baseline in Treatment-emergent Laboratory Parameter: Thyroid Stimulating Hormone
Tidsramme: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in treatment-emergent laboratory parameter: thyroid stimulating hormone during DB period was reported. Any abnormality occurring or worsening at or after the DB study treatment start date through the DB study treatment end date plus 3 days was considered to be treatment-emergent. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Change From Baseline in Treatment-emergent Laboratory Parameter: Hemoglobin
Tidsramme: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in treatment-emergent laboratory parameter: hemoglobin during DB period was reported. Any abnormality occurring or worsening at or after the DB study treatment start date through the DB study treatment end date plus 3 days was considered to be treatment-emergent. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Change From Baseline in Treatment-emergent Laboratory Parameter: Platelets, Leukocytes
Tidsramme: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in treatment-emergent laboratory parameter: platelets, leukocytes during DB period was reported. Any abnormality occurring or worsening at or after the DB study treatment start date through the DB study treatment end date plus 3 days was considered to be treatment-emergent. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Change From Baseline in Treatment-emergent Laboratory Parameter: Electrolytes (Sodium, Potassium, Calcium, Bicarbonate and Chloride)
Tidsramme: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in treatment-emergent laboratory parameter: electrolytes (sodium, potassium, calcium, bicarbonate and chloride) during DB period was reported. Any abnormality occurring or worsening at or after the DB study treatment start date through the DB study treatment end date plus 3 days was considered to be treatment-emergent. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Change From Baseline in Treatment-emergent Laboratory Parameter: Transaminases (Alanine Aminotransferase [ALT] and Aspartate Aminotransferase [AST])
Tidsramme: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in treatment-emergent laboratory parameter: transaminases (ALT and AST) during DB period was reported. Any abnormality occurring or worsening at or after the DB study treatment start date through the DB study treatment end date plus 3 days was considered to be treatment-emergent. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Change From Baseline in Treatment-emergent Laboratory Parameter: Bilirubin
Tidsramme: Baseline (Day 1), Weeks 24, 48, 72, and 96
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Change from baseline in treatment-emergent laboratory parameter: bilirubin during DB period was reported. Any abnormality occurring or worsening at or after the DB study treatment start date through the DB study treatment end date plus 3 days was considered to be treatment-emergent. The baseline value was the last non-missing assessment obtained before or on the DBSD. |
Baseline (Day 1), Weeks 24, 48, 72, and 96
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Double-blind Period: Time to First Clinical Event Committee (CEC)-Confirmed Hospitalization or Death for Pulmonary Arterial Hypertension (PAH)
Tidsramme: Placebo arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 199 weeks); Selexipag arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 213 weeks)
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Time to first CEC-confirmed hospitalization or death for PAH was calculated as the onset date of the first CEC-confirmed death or hospitalization due to PAH minus date of randomization+1 day. Kaplan-Meier method was used for estimation. |
Placebo arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 199 weeks); Selexipag arm: Randomization (Day 1) up to 7 days after last dose in the DB treatment (maximum up to 213 weeks)
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Double-blind Period: Dose-normalized Steady-state Trough Concentrations (Ctrough,ss,dn) of Selexipag and Its Metabolite ACT-333679 by Age Cohort
Tidsramme: Cohort (C) 1: Predose between Week (W) 16 to end of DB treatment period (maximum up to W212); C 2: Predose between Week 16 to end of DB treatment period (maximum up to W198); C 3: Predose between Week 16 to end of DB treatment period (maximum up to W96)
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Dose-normalized trough plasma concentration at steady-state (Ctrough,ss,dn) was defined as the plasma concentration just prior to the morning dose, with the last study intervention administration one day prior to the PK sampling. Steady-state was considered achieved if the participant has received a stable dose for at least 3 days prior to collection of the plasma sample. PK samples were collected at two protocol-specified visits per participant occurring between Week 16 and end of DB treatment period. Exact visit timing varied by participant. |
Cohort (C) 1: Predose between Week (W) 16 to end of DB treatment period (maximum up to W212); C 2: Predose between Week 16 to end of DB treatment period (maximum up to W198); C 3: Predose between Week 16 to end of DB treatment period (maximum up to W96)
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Double-blind Period: Dose-normalized Steady-state Trough Concentrations (Ctrough,ss,dn) of Selexipag and Its Metabolite ACT-333679 by Body Weight (BW)
Tidsramme: BW >=50kg: Predose between W16 to end of DB treatment period (maximum up to W212); BW >=25-<50kg: Predose between W16 to end of DB treatment period (maximum up to W198); BW >=9- <25kg: Predose between W16 to end of DB treatment period (maximum up to W175)
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Dose-normalized steady-state trough concentration (Ctrough,ss,dn) was defined as the plasma concentration just prior to the morning dose, with the last study intervention administration one day prior to the PK sampling. Steady-state was considered achieved if the participant has received a stable dose for at least 3 days prior to collection of the plasma sample. PK samples were collected at two protocol-specified visits per participant occurring between Week 16 and end of DB treatment period. Exact visit timing varied by participant. |
BW >=50kg: Predose between W16 to end of DB treatment period (maximum up to W212); BW >=25-<50kg: Predose between W16 to end of DB treatment period (maximum up to W198); BW >=9- <25kg: Predose between W16 to end of DB treatment period (maximum up to W175)
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Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Efterforskere
Efterforskere
- Studieleder: Actelion Clinical Trial, Actelion
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Studiestart
Primær færdiggørelse (Faktiske)
Primær færdiggørelse
Studieafslutning (Anslået)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- CR108716
- 2019-002817-21 (EudraCT nummer)
- AC-065A310 (Anden identifikator: Janssen Research & Development, LLC)
- 2022-501012-34-00 (Registry Identifier: EUCT number)
- 2019 (U.S. NIH-bevilling/kontrakt)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
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